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Background

The Early Breast Cancer Trialists' Collaborative Group meta-analysis demonstrated increased cardiac mortality among patients who received radiation therapy for breast cancer (RR = 1.27, P = 0.0001). However, many of the studies analyzed used radiation techniques that delivered a substantially higher dose to the heart than modern radiation therapy.

Studies using modern radiotherapeutic techniques have been conflicting. Several studies with median follow-ups of around 10 years have found no increase in heart disease with radiation therapy for breast cancer. Conversely, registry-based studies using the SEER database (RR 1.17) and the Ontario Cancer Registry (2% vs. 1% at 10 years, P = 0.02) demonstrated increased cardiac mortality.

Methods

Records were reviewed for 961 patients treated at the Hospital of the University of Pennsylvania with breast conserving therapy for stage I or II breast cancer between 1977-1994 and followed for a minimum of 2 years.

Comparison was made with respect to cardiac morbidity and mortality between patients radiated for left-sided versus right-sided breast tumors.

Radiation was delivered to the whole breast using tangential, coplanar, 6-15 MV photon fields for total tumor bed doses of 60 to 72 Gy (median 64 Gy). In both groups, 74% of the patients were treated with tangential beams alone, and 26% were treated with supraclavicular fields as well as tangential beams. The internal mammary nodes (IMNs) were treated in 14% of left-sided patients and 11% of right-sided patients, usually via wide tangential fields.

Results

There were no significant differences in overall survival or disease-free survival.

There was a trend towards increased cardiac deaths in the group irradiated to the left side (P = 0.22): 3.5% cardiac death among left-sided vs. 2.0% cardiac death among right-sided.

The relative-risk of cardiac events in the left-sided group increased with time: 1.9 vs. 1.5 at 10 years, 6.4 vs. 3.6 at 20 years.

There was no significant difference in rates of congestive heart failure, palpitations, arrhythmias, atrial fibrillation, mitral valve prolapse, or other valve disorders.

Hypertension appeared to decrease the relative impact of left-sided radiation on the risk of cardiac morbidity. Whereas left-sided radiation increased the risk of cardiac morbidity by a factor of 4.6 in patients without hypertension, it increased the risk by a factor of only 1.6 among hypertensive patients.

The use of an internal mammary node field, which directs additional radiation through the heart, was associated with a significant increase in coronary artery disease (18% vs. 7%, P < 0.001) and myocardial infarction (9% vs. 3%, P < 0.01).

Discussion

This study contributes additional evidence to the literature that radiation therapy for left-side breast cancers increases the risk of cardiac morbidity and possibly even mortality. It corroborates previous findings that the increase in risk manifests itself more fully in the second decade following radiation therapy versus the first.

The data reported will assist clinicians in balancing the risks of more aggressive radiation against those of more conservative, heart-sparing radiation techniques. Of note, few of the patients in this study received doxorubicin or trastuzumab; the risk of cardiac events may be further increased in breast cancer patients managed with contemporary treatment.

Conclusions

The reduction in relapse afforded by radiation therapy must be balanced against potential long-term cardiac morbidity when planning the technical aspects of treatment.

Patients treated with radiation therapy for left-sided breast cancer merit added vigilance in the prevention and diagnosis of cardiac disease.